Art v 1 and Amb a 4 Co-Sensitization Identifies Italian Patients at Risk for Mugwort-Celery-Spice Syndrome.

Abstract

Pollen defensins such as Art v 1 (mugwort) and Amb a 4 (ragweed) are pivotal allergens in pollen-food syndromes, but their clinical role in Southern Europe is poorly defined. To characterize sensitization to defensins and related allergens in Italy and its association with clinical phenotypes. Between 2021 and 2025, 7176 patients underwent molecular testing in three Italian centers. Sensitization to the pollen defensins Art v 1 and Amb a 4 was evaluated, together with celery allergens representing different protein families: the PR-10 Api g 1, the nsLTPs Api g 2, Api g 6, and the defensin Api g 7 (tested in a subset). Panallergens were also assessed. Defensin sensitization occurred in 272 patients (3.8%). Art v 1 mono-sensitization (64.7%) was largely confined to respiratory disease. Dual Art v 1-Amb a 4 sensitization (30.5%) identified a distinct subgroup at high risk of food reactions (OR = 6.9; p < 0.0001). Amb a 4 sensitization followed a clear northward gradient. Among 90 patients tested for Api g 7, 82.7% were positive, all co-sensitized to Art v 1, and one-third also to Amb a 4. IgE inhibition confirmed Art v 1 as the primary sensitizer driving defensin cross-reactivity. In contrast, Api g 2 nsLTP sensitization was strongly associated with severe systemic reactions. Defensin sensitization in Italy reveals distinct molecular and geographic signatures. Isolated Art v 1 sensitization dominates and marks respiratory allergy, while co-sensitization to Amb a 4-often associated with Api g 7 co-recognition-defines patients at high risk for systemic food reactions.